Is HSDB 3364 Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use HSDB 3364? Is HSDB 3364 safe for nursing mother and child? Does HSDB 3364 extracts into breast milk? Does HSDB 3364 has any long term or short term side effects on infants? Can HSDB 3364 influence milk supply or can HSDB 3364 decrease milk supply in lactating mothers?

Ergot derivative which is used in the prevention and treatment of postpartum hemorrhage. It is not excreted into breast milk in clinically significant amount (Erkkola 1978) and, besides the information offered by the manufacturer, no reliable publications were found about problems in infants whose mothers were treated. There is a controversy on an antiprolactin effect and its ability to decrease milk production found by some authors (Peters 1979, Döner 1979, Weiss 1975).Some have published an association with a decreased in duration of breastfeeding though not in the percentage of initiation (Brown 2014, Jordan 2009) nor a decrease in weight gaining (Arabin 1986).Others did not find a decrease in prolactin level (Javier del Castillo 1985, Del Pozo 1975), nor difference in the rate of exclusive breastfeeding or monthly weight gain (González1984), considering that the treatments limited to the first week postpartum that use a low dose do not affect lactation or the infant. It has frequent side effects (nausea, vomiting, headache, hypertension) that do not occur with oxytocin, so the latter is preferable to reduce the risk of postpartum hemorrhage. There are insufficient data to know whether immediate breastfeeding is effective for this type of prevention (Chelmow 2011).They have occurred serious poisonings in infants when giving directly both orally or intramuscularly due to confusion with other medication for newborns (Aeby 2003).

Limited information indicates that maternal doses of HSDB 3364 up to 0.75 mg daily produce low levels in milk. Product labeling in the U.S. currently recommends avoiding breastfeeding for 12 hours following the last dose of HSDB 3364. This warning appears to be based on unpublished adverse reactions in breastfed infants after several days of maternal HSDB 3364 therapy. The use of shorter courses of the drug after delivery during the colostral phase of lactation are not expected to transfer appreciable amounts of drug to the breastfed infant or risk adverse effects in the infant. The lack of infant side effects was documented in one case-control study. Long courses of HSDB 3364, especially after the milk comes in, are best avoided in mothers who wish to nurse. When they are required, withholding breast feeding for 12 hours following the last dose of HSDB 3364 is prudent. If adverse reactions in the breastfed infant are seen, such as tachycardia, vomiting, diarrhea or agitation, the drug should be discontinued. Some sources recommend avoiding HSDB 3364 altogether during breastfeeding.[1] Although results of several imperfect studies are somewhat mixed, it appears that HSDB 3364 can decrease serum prolactin and possibly the amount of milk production and duration of lactation, especially when used in the immediate postpartum period. The effect seems to be related to the dosage and route of administration, with injected doses having a greater impact than oral. A short course immediately postpartum does not appear to have a detrimental effect on lactation.

According to the manufacturer, there are isolated reports of adverse effects in breast-fed infants whose mothers were receiving HSDB 3364 for several days. One or more of the following symptoms were observed during HSDB 3364 therapy and disappeared upon withdrawal of the medication: elevated blood pressure, bradycardia, tachycardia, vomiting, diarrhea, restlessness, or clonic cramps. Another case reported to the manufacturer was a breast-fed infant who presented with seizures after about 4 to 6 days of maternal HSDB 3364 therapy. The infant's seizures began on the second day of treatment of the mother after breastfeeding. Medications were discontinued per the mother. The infantile seizures resolved about six weeks later.[6] It is not possible to determine the causality of any of the adverse effects with the information available. A working group of the French national medication safety agency (ANSM) reported 23 cases of infants exposed to HSDB 3364 via breastmilk who had a total of 44 adverse reactions. (Some of these might be the same as those reported in the previous paragraph.) The working group considered tachycardia, vomiting, diarrhea and agitation to be sufficiently well documented to add to the prescribing information.[7] A prospective case-control study compared the outcome of infants whose mothers had taken HSDB 3364 postpartum 0.125 mg 2 times daily for 5 days or 3 times daily for 3 days to mothers who had taken amoxicillin which served as a control group. Of 29 mothers who had taken HSDB 3364, there were no differences in neonatal health or development at follow-up at 17 months postpartum between the treatment and control groups.[8]

Oral HSDB 3364 in a dose of 0.2 mg 3 times daily for 7 days in 10 postpartum subjects caused no difference in serum prolactin concentrations from placebo administered to 10 postpartum control women. No significant difference found in the daily milk volumes between the groups.[9] A single intramuscular injection of HSDB 3364 0.2 mg given to 4 women on day 3 postpartum caused a decrease in serum prolactin beginning 45 to 60 minutes after the dose. For 2 to 3 hours after the dose, serum prolactin levels remained about 50% lower than baseline levels.[10] A single intramuscular injection of HSDB 3364 0.2 mg was given to 14 women during the first 1.5 hours postpartum. At 80 to 90 minutes after the injection, the normal postpartum rise in serum prolactin was 56% in the women who received HSDB 3364 compared to a 285% in serum prolactin in women who received a placebo injection. Six treated women had no increase in serum prolactin compared to 2 of the control women.[11] Thirty women who delivered fullterm infants received a single intramuscular dose of HSDB 3364 0.2 mg after delivery, followed by oral ergotamine 1 mg 3 times daily for 6 days. Compared to 28 women who delivered fullterm infants and received no ergot derivatives, there was no difference in the milk production, as measured by weight differences before and after nursing, between the 2 groups during the first 6 days postpartum.[12] Thirty postpartum women were given HSDB 3364 0.2 mg orally 3 times daily for the first 7 days postpartum. Baseline (prior to nursing) serum prolactin was no different from those of 30 postpartum women who received no HSDB 3364 on days 1 and 3 postpartum. However, on day 7 postpartum, serum prolactin levels were significantly less in the treated women. Milk production was also reduced in the treated women on days 3 and 7 postpartum compared to controls.[13] Ten women received a single intravenous dose of 0.4 mg of HSDB 3364 immediately postpartum were compared to 10 control mothers who received no HSDB 3364; all women received a continuous infusion of oxytocin postpartum. None of the women were allowed to nurse or extract milk from their breasts or to receive hormones to suppress lactation. Serum prolactin measured during labor, immediately after administration of the drug and daily at 9 am for 5 days postpartum found no statistical differences in prolactin levels between the 2 groups.[14] In a randomized study, 48 patients were given HSDB 3364 0.125 mg orally every 8 hours for the first 7 days postpartum. Another 44 in the same hospital were not given HSDB 3364. No statistical differences were found in the serum levels of prolactin at 3 days postpartum between the groups, although women with normal deliveries had higher prolactin levels than those delivered by cesarean section. At 1 month postpartum, no differences were found in the percentage of exclusive breastfeeding or in the weight gain of infants.[15] In a prospective, randomized study, 444 postpartum mothers were given 0.125 mg of HSDB 3364 3 times a day, while 436 were given placebo. Milk production among untreated women averaged 880 grams during the first 6 days, while among treated patients it was only 563 grams. After 4 weeks there were still differences in the quantity of milk produced.[16] A prospective case-control study compared lactation in mothers had taken HSDB 3364 postpartum 0.125 mg 2 times daily for 5 days or 3 times daily for 3 days to mothers who had taken amoxicillin which served as a control group. The rates of exclusive breastfeeding and reports of decreased lactation were not significantly different in the two groups.[8]